2021-30/July 26
Contributors: Ruth Birbe, William Rafferty

A female patient in her mid-60s presents with an incidental 1.7 cm left kidney mass on CT. A robotic-assisted partial nephrectomy shows a well-circumscribed not encapsulated tan solid nodule with small cystic foci, confined to the kidney (stage pT1a)


1. What is the correct diagnosis?

a. Chromophobe renal cell carcinoma with squamous differentiation

b. Alveolar soft part sarcoma

c. Biphasic papillary renal cell carcinoma

d. Invasive urothelial carcinoma with squamous differentiation of the renal pelvis

e. Metanephric adenoma


2. What immunohistochemical stain profile is characteristic in this entity?

a. TFE3 +, MyoD1 +, PAS + diastase resistant

b. Cyclin D1 +, alpha methyl Co-A racemase +, CK7 +, CK-903 +, CD117-

c. P63 +, GATA3 +, uroplakin +, PAX8 -, high molecular weight keratin +

d. Vimentin –, CD117 +, e-cadherin +, CK7 +, hales colloidal iron +

e. WT1 +, CD57+, alpha methyl Co-A racemase –

1. c; 2. b

Biphasic papillary renal cell carcinoma (BPRCC)

Biphasic papillary renal cell carcinoma (BPRCC) is a variant of papillary renal cell carcinoma first described in 2012 and not currently on the WHO classification. Other synonyms include biphasic alveolosquamoid renal carcinoma, and biphasic squamoid alveolar renal cell carcinoma due to the dual or biphasic cell population.

The tumor is grossly white to tan brown and frequently multifocal. Microscopically, it is solid compact with small cystic areas. There is a characteristic biphasic morphology with two-cell population, a larger eosinophilic “squamoid” cells with abundant cytoplasm and higher-grade nuclei surrounded or admixed with a smaller cell population of cuboidal and amphophilic cells with scanty cytoplasm. Psammoma bodies and macrophages are also present. There is no evidence of keratin pearls or true squamous phenotype, with negative CK5/6 and P63, hence the designation of “squamoid” cells.

The squamoid cell clusters have a characteristic alveolar, glomeruloid or micronodular architecture with cytophagocytosis (reported as emperipolesis) of apoptotic neutrophilic granulocytes, cell fragments, and debris. They are negative for the squamous markers CK5/6 and p63; and exclusively positive for cyclin-D1 (BCL-1) and, while the smaller cells surround the clusters are negative. In our case, the squamoids cells were also exclusively positive for high molecular weight keratin (CK-903). CD57 expression has also been reported limited to the squamoid cells. There is an opposite staining pattern with RCC in this case, where RCC is limited to the smaller cells (image 5).

BPRCC is uniformly positive for EMA, CAM5.2, pancytokeratin, alpha methyl Co-A racemase, and PAX8; variable positive for CD10 and 34βE12 (CK-903); and negative for carbonic anhydrase 9, CD117, GATA-3, WT1, CK5/6, and CK20, vimentin, parvalbumin, S100 protein, S100 A1, p63, p53, CDX2, uroplakin III, HMB45, TFE3, WT1, synaptophysin, chromogranin A, thyroglobulin, and TTF1. The Ki67 proliferation index has been reported higher on the squamoid cells (more than 5% up to 25%). Ultrastructurally, the squamoid cells have desmosomes and tonofilaments.

BPRCC can be bilateral, multifocal and associated with papillary adenomas, other papillary RCCs, clear cell RCC, and low-grade urothelial carcinoma.

The genetic profile can be similar to other papillary RCCs with gain of chromosome 7 and 17 and loss of chromosome Y, as well as multiple chromosomal aberrations in regions of known tumor suppressor genes and oncogenes. MET alterations support BPRCC as a morphological variant of type 1 papillary RCC.

The survival data is limited since BPRCC is a newly described entity, with a series reporting metastatic disease in 24% of the cases; and metastasis, recurrence, or death due to the disease in 15% of patients.

The differential diagnosis includes papillary renal cell carcinoma, type 2 and oncocytic variant (Cyclin D1-); metanephric adenoma (option e. WT1 +, CD57+, alpha methyl Co-A racemase -, EMA -, CK7 -); urothelial carcinoma with squamous differentiation (option c. P63 +, GATA3 +, uroplakin +, PAX8 -, high molecular weight keratin +); chromophobe renal cell carcinoma with squamous differentiation (option d. vimentin –, CD117 +, e-cadherin +, CK7 +, hales colloidal iron +); alveolar soft part sarcoma (option a. TFE3 +, MyoD1 +, PAS + diastase resistant); and mucinous tubular and spindle cell carcinoma (PAX8 +, EMA +, CK-903, stroma + for alcian blue, NSE, synaptophysin, chromogranina, PSA).

Biphasic papillary renal cell carcinoma is a rare variant of papillary renal cell carcinoma with squamoid cyclin-D1 (BCL-1) positive cells, multifocality, small tumor size, and indolent but potentially aggressive behavior.

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Ruth Birbe; William Rafferty
Cooper University Hospital-MD Anderson Cancer Center


kidney; Biphasic squamoid papillary RCC; cyclin-D1; BCL-1